Our understanding of the role of hippocampus in learning and memory has undergone many changes in recent years. Of particular interest is the realization that hippocampus is essential to encoding specific relationships between behavioral or cognitively relevant events. For the past 5 years, this project has examined how the process of encoding and recalling information in hippocampal ensembles is utilized in short-term (i.e delayed-non-match/match-to-sample [DNMS/DMS]) memory and how that process is disrupted following exposure to the psychoactive drug, marijuana (i.e. cannabinoids). The latter observation is not trivial since the cannabinoid has a high receptor density in hippocampus and with its endogenous ligands is capable of "sculpting", refining or even blocking hippocampal-dependent memory. In the last funding period several technological and computational methods were developed and applied to hippocampal neuronal recording which allowed insight into how ensembles of hippocampal neurons encode information. This Research Project will continue to investigate hippocampal mechanisms of information processing by: (1) characterizing the transference of information within the ensemble from the encoding to the decision- making phase as required to select the appropriate trial specific behavioral response; (2) examining the basis of two types of behavioral errors which likely result from insufficient encoding of transference of such information; (3) further analyzing the topographical organization within the hippocampus with respect of anatomic distribution of different functional cell types for different types of tasks; (4) determining the significance of cannabinoid receptor modulation if GABAergic interneuron activity in hippocampus and its relation to previously reported dose-dependent attenuation of information encoding in DNMS/DMS tasks by acute cannabinoids, and (5) incorporating electrophysiological analyses in the assessment of behavioral tolerance to the acute effects of cannabinoids on memory that develop following chronic exposure to the drug.